Upregulated periostin promotes angiogenesis in keloids through activation of the ERK 1/2 and focal adhesion kinase pathways, as well as the upregulated expression of VEGF and angiopoietin‑1

Zhang,Zhe; Nie,Fangfei; Chen,Xinlei; Qin,Zelian; Kang,Chunfu; Chen,Bin; Ma,Jianxun; Pan,Bolin; Ma,Yongguang

doi:10.3892/mmr.2014.2827

Upregulated periostin promotes angiogenesis in keloids through activation of the ERK 1/2 and focal adhesion kinase pathways, as well as the upregulated expression of VEGF and angiopoietin‑1

Authors:
- Zhe Zhang
- Fangfei Nie
- Xinlei Chen
- Zelian Qin
- Chunfu Kang
- Bin Chen
- Jianxun Ma
- Bolin Pan
- Yongguang Ma
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Affiliations: Department of Plastic Surgery, Peking University Third Hospital, Beijing 100191, P.R. China
Published online on: October 31, 2014 https://doi.org/10.3892/mmr.2014.2827
Pages: 857-864
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Periostin, a secreted extracellular matrix protein, is highly expressed in wound healing and in various types of human cancer and is involved in angiogenesis. Keloids, considered dermal benign tumors, are granulomatous lesions characterized by capillary proliferation. However, the underlying regulatory mechanism of angiogenesis in keloids remains to be elucidated. The present study aimed to examine the effect of periostin on angiogenesis in keloids. The expression of periostin was upregulated and the vessel density was higher in human keloids compared with normal tissue, observed following staining with CD31 and CD105. Periostin demonstrated a markedly positive correlation with blood vessel density, which was assessed using CD31 staining (r=0.711; P<0.01) and a weak correlation was observed using CD105 staining (r=0.251; P<0.01). Conditioned medium from keloid fibroblasts (KFs) promoted the migration and tube formation of human umbilical vein endothelial cells (HUVECs) compared with normal fibroblasts and this effect may have been abrogated by the short hairpin RNA knockdown of periostin. Treatment with recombinant human periostin promoted the migration and tube formation of HUVECs by activating the extracellular signal‑regulated kinase 1/2 and focal adhesion kinase signaling pathway. In addition, periostin increased the secretion of vascular endothelial growth factor and angiopoietin‑1 in the KFs. In conclusion, these data suggested that upregulation in the level of periostin may promote angiogenesis directly and indirectly in keloids and may be a key factor in keloid development. Periostin may, therefore, be a promising therapeutic target in the treatment of keloids and other angioproliferative diseases.

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